Assessment of lung deposition and analysis of the effect of fluticasone/salmeterol hydrofluoroalkane (HFA) pressurized metered dose inhaler (pMDI) in stable persistent asthma patients using functional respiratory imaging.

BACKGROUND: Unambiguously for inhaled products, PK measures are best suited for ensuring that the total systemic exposure is equivalent for two products but cannot provide regional information about lung deposition and structural changes. Functional respiratory imaging (FRI) has been demonstrated to be sensitive for distinguishing small but imperative differences related to a single treatment. METHODS: In this study FRI is used in 16 asthmatic patients to assess equivalence in regional deposition for two products (fluticasone/salmeterol, test and reference) by directly measuring regional functional and structural changes within the lungs following its administration. RESULTS: No differences were observed between the lung deposition patterns and the effects on lung structure and function of two products, having the same formulation and manufactured by different organizations using FRI. CONCLUSIONS: Results using FRI complement PK assessments. The added value of this approach to the conventional clinical methods could be significant.

The effects of long-term noninvasive ventilation in hypercapnic COPD patients: a randomized controlled pilot study.

INTRODUCTION: Noninvasive ventilation (NIV) is a well-established treatment for acute-on- chronic respiratory failure in hypercapnic COPD patients. Less is known about the effects of a long-term treatment with NIV in hypercapnic COPD patients and about the factors that may predict response in terms of improved oxygenation and lowered CO(2) retention. METHODS: In this study, we randomized 15 patients to a routine pharmacological treatment (n = 5, age 66 [standard deviation ± 6] years, FEV(1) 30.5 [±5.1] %pred, PaO(2) 65 [±6] mmHg, PaCO(2) 52.4 [±6.0] mmHg) or to a routine treatment and NIV (using the Synchrony BiPAP device [Respironics, Inc, Murrsville, PA]) (n = 10, age 65 [±7] years, FEV(1) 29.5 [±9.0] %pred, PaO(2) 59 [±13] mmHg, PaCO(2) 55.4 [±7.7] mmHg) for 6 months. We looked at arterial blood gasses, lung function parameters and performed a low-dose computed tomography of the thorax, which was later used for segmentation (providing lobe and airway volumes, iVlobe and iVaw) and post-processing with computer methods (providing airway resistance, iRaw) giving overall a functional image of the separate airways and lobes. RESULTS: In both groups there was a nonsignificant change in FEV(1) (NIV group 29.5 [9.0] to 38.5 [14.6] %pred, control group 30.5 [5.1] to 36.8 [8.7] mmHg). PaCO(2) dropped significantly only in the NIV group (NIV: 55.4 [7.7] → 44.5 [4.70], P = 0.0076; control: 52.4 [6.0] → 47.6 [8.2], NS). Patients actively treated with NIV developed a more inhomogeneous redistribution of mass flow than control patients. Subsequent analysis indicated that in NIV-treated patients that improve their blood gases, mass flow was also redistributed towards areas with higher vessel density and less emphysema, indicating that flow was redistributed towards areas with better perfusion. There was a highly significant correlation between the % increase in mass flow towards lobes with a blood vessel density of >9% and the increase in PaO(2). Improved ventilation-perfusion match and recruitment of previously occluded small airways can explain the improvement in blood gases. CONCLUSION: We can conclude that in hypercapnic COPD patients treated with long-term NIV over 6 months, a mass flow redistribution occurs, providing a better ventilation-perfusion match and hence better blood gases and lung function. Control patients improve homogeneously in iVaw and iRaw, without improvement in gas exchange since there is no improved ventilation/perfusion ratio or increased alveolar ventilation. These differences in response can be detected through functional imaging, which gives a more detailed report on regional lung volumes and resistances than classical lung function tests do. Possibly only patients with localized small airway disease are good candidates for long-term NIV treatment. To confirm this and to see if better arterial blood gases also lead to better health related quality of life and longer survival, we have to study a larger population.